Ketamine Offers Hope Against Treatment-Resistant Bipolar Depression, New Study Finds

• Ketamine reduced depressive symptoms
• Trial included 68 patients
• Potential benefits require further study

People with treatment-resistant bipolar depression may have another potential option for managing symptoms that persist despite conventional medications.

A new clinical trial found that multiple low-dose intravenous ketamine infusions significantly reduced depressive symptoms in some patients with bipolar I or bipolar II disorder.

The findings, published in JAMA Psychiatry and reported by Medical Xpress and Medscape, are particularly relevant because of concerns that ketamine could trigger mania, hypomania, or psychosis in people with bipolar disorder.

However, researchers warn that the study was relatively small and short, leaving unanswered questions about the treatment’s long-term safety and effectiveness.

What Did Researchers Discover About Ketamine?

The Ket-BD trial included 68 adults with moderate or severe treatment-resistant bipolar depression who had tried at least two evidence-based drug treatments without sufficient improvement.

The participants had particularly complex treatment histories: According to data cited by Medscape, they had taken an average of approximately 11 medications during their lifetimes and six during their current depressive episodes.

All participants continued taking stable doses of at least one mood stabilizer or antipsychotic throughout the study.

Over two weeks, they received four 40-minute intravenous infusions of either ketamine or midazolam, a sedative used as the comparison treatment.

The results showed a significant difference:

• 35% of participants receiving ketamine experienced a reduction of at least half in their depressive symptoms.
• Approximately 12% achieved that response with midazolam.
• The remission rate was 17.6% with ketamine, compared with 8.8% for the comparison treatment.
• By day 14, the depression score was 7.3 points lower in the ketamine group.

That difference exceeded the 3.6-point threshold researchers had previously established as the minimum needed for the result to be considered clinically significant.

Ket-BD Trial Reports No Treatment-Related Mania or Psychosis

One of the main concerns about using ketamine in people with bipolar disorder is its potential to trigger mania, hypomania, or psychotic symptoms.

During the trial, researchers reported no treatment-related cases of mania, hypomania, or psychosis and no suicide attempts.

One patient in each group developed mixed features, meaning they experienced some hypomanic symptoms without meeting the clinical criteria for hypomania.

However, this does not mean the risk can be ruled out.

John Krystal, chair of the Department of Psychiatry at Yale School of Medicine, who was not involved in the research, told Medscape that 34 patients per group were insufficient to establish ketamine’s safety in this population definitively.

Additionally, every participant continued taking mood stabilizers or antipsychotics, which may have helped reduce the risk of developing mania.

How Long Did Ketamine’s Effects on Treatment-Resistant Bipolar Depression Last?

This is one of the main limitations of the treatment observed in the study.

Ketamine’s antidepressant benefit lasted approximately one week after the final infusion, but the symptoms then began returning gradually.

Adverse effects were concentrated primarily on infusion days, and patients receiving ketamine experienced more episodes of dissociation during administration.

Therefore, the next major question is how to maintain the initial improvement.

The team led by psychiatrist Joshua Rosenblat of University Health Network and the University of Toronto says larger trials and studies evaluating maintenance treatments or potential booster doses are necessary.

What Does the Ketamine Study Mean for Patients?

The findings offer a promising but preliminary signal for people whose bipolar depression does not improve sufficiently with available treatments.

Steve Strakowski, a professor of psychiatry at Indiana University School of Medicine who was not involved in the study, also noted that researchers must examine patients with bipolar I and bipolar II disorder separately because of the differences between the conditions.

The ketamine used in the trial was administered intravenously at controlled doses in a clinical setting, while participants continued receiving other psychiatric treatments.

The study does not mean that someone with bipolar disorder should use ketamine independently or discontinue their current medications.

Any such treatment requires evaluation, a prescription, and monitoring by specialized healthcare professionals.

The research opens a potential new avenue for treating one of the most difficult forms of bipolar depression, but a fundamental question remains: How can the initial improvement be made safe and lasting?

Warning: This information is for informational and educational purposes only and does not replace diagnosis, treatment, or guidance from a healthcare professional. Ketamine should be administered only under medical supervision and should never be used independently.

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SOURCE: JAMA Psychiatry / Medical Xpress / Medscape Medical News / Medical Dialogues